Objective:To compare the short-term effect and adverse reaction of venetoclax(VEN)combined with azacitidine(AZA)versus"7+3"regimen in newly diagnosed elder patients with acute myeloid leukemia(AML).Methods:From January 2021 to January 2022,the clinical data of seventy-nine newly diagnosed elder patients with AML at the Second Hospital of Shanxi Medical University and the Shanxi Bethune Hospital were retrospectively analyzed,including VEN+AZA group(41 cases)and"7+3"group(38 cases).The propensity score matching(PSM)method was used to balance confounding factors,then response,overall survival(OS),progression-free survival(PFS)and adverse reactions between the two groups were compared.Results:The ORR of VEN+AZA group and"7+3"group was 68％and 84％,respectively,and the CRc was 64％and 72％,respectively,the differents were not statistically significant(P＞0.05).In the VEN+AZA group,there were 5 non-remission(NR)patients,4 with chromosome 7 abnormality(7q-/-7),and 1 with ETV6 gene mutation.Median followed-up time between the two groups was 8 months and 12 months,respectively,and the 6-months OS was 84％vs 92％(P=0.389),while 6-months PFS was 84％vs 92％(P=0.258).The main hematological adverse reactions in two groups were stage Ⅲ-Ⅳmyelosuppression,and the incidence rate was not statistically different(P＞0.05).The median time of neutrophil recovery in two groups was 27(11-70)d,25(14-61)d(P=0.161),and platelet recovery was 27(11-75)d,25(16-50)d(P=0.270),respectively.The infection rate of VEN+AZA group was lower than that of"7+3"group(56％vs 88％,P=0.012).The rate of lung infections of two groups was 36％and 64％,respectively,the difference was statistically significant(P=0.048).Conclusion:The short-term effect of VEN+AZA group and"7+3"regimens in eldrly AML patients are similar,but the VEN+AZA regimen had a lower incidence of infection.The presence of chromosome 7 abnormality(7q-/-7)may be a poor prognostic factor for elderly AML patients treated with VEN+AZA.

Acute myeloid leukemia (AML) has highly heterogeneous clinical manifestations and poor prognosis, and traditional chemotherapy is the main treatment. In recent years, with the in-depth development of next-generation sequencing technology, the treatment of AML is gradually exploring the precise targeted therapy in the direction of molecular biology and immunophenotype. The advent of various small-molecule inhibitors and immune-targeted drugs has brought hope to patients who cannot tolerate intensive chemotherapy or with relapsed/refractory AML. Compared with traditional chemotherapy, targeted therapy has the advantages of significant curative effect and fewer adverse effects. This article reviews the latest research progress of targeted drug therapy for AML.
Humans ; Leukemia, Myeloid, Acute/drug therapy* ; Immunotherapy ; Immunotherapy, Adoptive ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use*

Objective To investigate the bacterial community diversity in Dermatophagoides farinae. Methods Laboratory-cultured D. farinae was collected, and the composition of microbial communities was determined by sequence analyses of the V4 region in the bacterial 16S ribosomal RNA (16S rRNA) gene on an Illumina PE250 high-throughput sequencing platform. Following quality control and filtering of the raw sequence files, valid reads were obtained and subjected to operational taxonomic units (OTU) clustering and analysis of the composition of microbial communities and alpha diversity index using the Usearch software, Silva database, and Mothur software. Results A total of 187 616 valid reads were obtained, and 469 OTUs were clustered based on a sequence similarity of more than 97%. OTU annotation showed that the bacteria in D. farinae belonged to 26 phyla, 43 classes, 100 orders, 167 families and 284 genera. The bacteria in D. farinae were mainly annotated to five phyla of Proteobacteria, Firmicutes, Bacteroidota, Actinobacteriota, and Acidobacteriota, with Proteobacteria as the dominant phylum, and mainly annotated to five dominant genera of Ralstonia, norank-f-Mitochondria, Staphylococcus and Sphingomonas, with Wolbachia identified in the non-dominant genus. Conclusions A high diversity is identified in the composition of the bacterial community in D. farinae, and there are differences in bacterial community diversity and abundance among D. farinae.

Objective: To understand the current situation regarding pediatric off-label use of drugs recommendations in Chinese clinical practice guidelines and to make recommendations for standardized reporting format regarding off-label use of drugs for children. Methods: This cross-sectional study was carried out by systematically searching the databases for Chinese guideline consensus articles published in journals between 2018 and 2020 and extracting recommendations regarding off-label use of drugs from those articles. The essential characteristics of the included guidelines, the ranking of off-label drug types, the order of drug information, the type of off-label drug use, and the percentage of citation studies on which the recommendations were based were analyzed. Results: Among 108 studies that included Chinese off-label guidelines and consensus, 364 recommendations on pediatric off-label use of drugs were included. The Chinese Medical Association published the most, 48 out of the 108 studies (44.4%), and of those 14 studies (13.0%) were on infectious and parasitic diseases. Of the 364 recommendations on off-label use of drugs, the most commonly addressed drugs were 16 recommendations (4.4%) for cyclosporine A, 11 recommendations (3.0%) for methotrexate , and 11 recommendations (3.0%) for fentanyl. The most commonly addressed drug categories were as follows: 68 recommendations (18.6%) were immune system drugs, 66 recommendations (18.1%) were anti-infectives, and 56 recommendations (15.4%) were oncology drugs. The most commonly addressed drug information accounts were as follows: 364 recommendations (100.0%) were indications, 204 recommendations (56.0%) were dosages, and 198 recommendations (54.4%) were the route of administration. Based on the instructions approved by the Chinese Food and Drug Administration, the main forms of the off-label drug were as follows: 175 recommendations (48.1%) were unapproved indications, 127 recommendations (34.9%) were unapproved populations, and 72 recommendations (19.8%) were unapproved ages. Only 129 recommendations (35.4%) were cited, mainly including clinical guidelines (48 studies, 23.4%), reviews (22 studies, 10.7%), and pediatric randomized controlled trials (22 studies, 10.7%). Conclusions: Off-label use of drugs is commonly recommended in pediatric guidelines and consensus documents written by Chinese authors. However, the reporting of the recommendations varies widely, and the quality of the supporting evidence is poor.
Child ; China ; Consensus ; Cross-Sectional Studies ; Humans ; Off-Label Use ; Pharmaceutical Preparations

OBJECTIVE: To evaluate whether ultrafine particulates (UFPs) have direct deleterious effects on cardiac function through activating MAPK signaling. METHODS: Langendorff-perfused Sprague-Dawley rat hearts were randomly divided into 2 groups (n=10/each group). In control group, the rat hearts were perfused with Tyrode's buffer for 40 min; in UFPs-treated group, the hearts were perfused with UFPs at a concentration of 12.5 mg/L. Cardiac function was determined by measuring left ventricular developed pressure (LVDP), left ventricular peak rate of contraction and relaxation (±dp/dt_max) and coronary flow (CF). The levels of malondialdehyde (MDA), superoxide dismutase (SOD), total anti-oxidant capacity (TAOC) were detected in order to evaluate cardiac oxidative stress via the thiobarbituric acid assay, water soluble tetrazolium salt assay and colorimetry, respectively. The expressions of p-p38 MAPK, p-ERKs and p-JNKs in the myocardium were observed using immunohistochemical staining and Western blots. RESULTS: No significant changes in cardiac function were detected before and after the perfusion in control group while UFPs perfused hearts showed a decline in cardiac function in a time-dependent manner (all P < 0.05). In UFPs-treated group, LVDP, +dp/dt_max, -dp/dt_max and CF were statistically reduced from (82.6±2.1) mmHg, (1 624±113) mmHg/s, (1 565±116) mmHg/s, (12.0±0.2) mL/min to (56.8±4.4) mmHg, (1 066±177) mmHg/s, (1 082±134) mmHg/s, (8.7±0.3) mL/min (all P < 0.05), respectively. Furthermore, The comparison between the two groups observed that UFPs perfusion caused a significant decrease in cardiac function at 30 and 40 min compared with the control group (all P < 0.05). At the end of the perfusion, the level of MDA was increased from (0.98±0.14) nmol/L to (1.95±0.18) nmol/L, while SOD and TAOC were reduced from (12.50±1.87) U/mL and (6.83±1.16) U/mL to (6.50 ±1.04) U/mL and (3.67±0.82) U/mL (all P < 0.001) in UFPs group, respectively. In coincidence with these changes, immunohistochemistry and Western blots results showed that the levels of p-p38 MAPK, p-ERKs and p-JNKs in the myocardium significantly increased in UFPs group as compared with control group (all P < 0.05). CONCLUSION The results of this study demonstrated that the short-term exposure of UFPs to the isolated rat hearts has direct and acute toxic effects on cardiac function, probably related to attenuation of anti-oxidative capacity and activation of MAPK signaling pathways.
Animals ; Heart ; Malondialdehyde/metabolism* ; Myocardium ; Oxidative Stress ; Rats ; Rats, Sprague-Dawley

Malocclusion is one of the three most common oral diseases reported by World Health Organization(WHO). In China, its incidence rate is rising. Malocclusion seriously affects the dental and maxillofacial function, facial appearance and growth development of nearly 260 million children in China, and what is more, it affects their physical and mental health development. Malocclusion occurrence is related to genetic and environmental factors. Early treatment of malocclusion can create a good dental and maxillofacial development environment, correct abnormal growth and control the adverse effects of abnormal genetic factors. It can effectively reduce the prevalence of children's malocclusion and enhance their physical and mental health. This is an urgent need from the economic perspective of our society, so it has great practical and social significance. Experts from the project group "standard diagnose and treatment protocols for early orthodontic intervention of malocclusions of children" which initiated by China National Health Institute of Hospital Administration wrote the "China Experts' Consensus on Preventive and Interceptive Orthodontic Treatments of Malocclusions of Children", which aims to guide and popularize the clinical practice, improve the clinical theory and practice level, and accelerate the disciplinary development of early treatment of children's malocclusion in China. The consensus elaborates the harmfulness of malocclusion and the necessity of early treatment, and brings up the principles and fundamental contents. Based on the law of dental and maxillofacial development, this paper puts forward the guiding suggestions of preventive and interceptive treatments in different stages of dental development ranging from fetus to early permanent dentition. It is a systematic project to promote and standardize the early treatment of malocclusion. Through scientific and comprehensive stratified clinical practice and professional training, the clinical system of early treatment of malocclusion in China will eventually be perfected, so as to comprehensively care for children's dental and maxillofacial health, and improve their oral and physical health in China.
Child ; China/epidemiology* ; Consensus ; Dental Care ; Humans ; Malocclusion/prevention & control* ; Orthodontics, Interceptive

Objective::To investigate the antihypertensive effect of Tianmu Jiangya powder and its related antihypertensive mechanism by using SHR rats as a model, and protein expressions provide an experimental basis for the clinical application of Tianmu Jiangya powder in the treatment of hypertension. Method::Sixty male SHR rats were randomly divided into six groups according to body weight after one week of adaptive feeding: model group, valsartan group (12 mg·kg^-1), captopril group (9 mg·kg^-1), hydrochlorothiazide group (6 mg·kg^-1), Tianmu Jiangya powder low and high-dose group (0.36, 1.44 g·kg^-1), WKY rats were used as the normal group, and the intragastric administration lasted for 16 weeks. Softron BP-2010A intelligent non-invasive blood pressure meter was used to measure the systolic blood pressure (SBP)and heart rate (HR) of rat tail arteries. Adobe Photoshop CS5 software was used to analyze the left auricle and claw fixed selected areas to evaluate the effect on blood stasis syndrome. Vevo 2100 small animal ultrasound imaging system detects left ventricular ejection fraction (LVEF), left ventricular shortening (FS), left ventricular end-systolic volume (LVESV), left ventricular end-diastolic volume (LVEDV), left ventricular end-systole dimension (LVIDs), left ventricular end-diastole dimension (LVIDd), interventricular septum end-systolic depth (IVSs), and interventricular septum end-diastolic depth (IVSd). Then the rats were sacrificed and the materials were taken (blood, heart, aorta, liver, kidney, tibia), and the weight of heart, liver, kidney and tibia length were measured and recorded. Hematoxylin-eosin (HE) staining was used to observe the pathological changes of the heart and thoracic aorta. Separation of serum and plasma, and determination of nitric oxide (NO) in serum by nitrate reductase method. Radioimmunoassay was used to detect plasma adrenaline/3 methoxyadrenaline (MN), urea (UREA), and uric acid (UA) contents. The expression of nitric oxide synthase(iNOS) and vascular endothelial growth factor(VEGF) protein in thoracic aorta of each group was detected and analyzed by immunohistochemical method. Result::Compared with normal group, the SBP and HR of the rats in model group were significantly increased (P<0.05). The r value of the claw was significantly reduced and the g value was significantly increased at 8 and 16 weeks (P<0.05). LVEF and FS significantly decreased, LVESV, LVIDs, IVSd increased significantly (P<0.05). Heart weight, heart weight /tibia length, liver weight and liver weight /tibia length, plasma of MN, UREA, and UA contents significantly increased, and promoted the expression of iNOS and VEGF proteins in the aortic (P<0.05). Compared with the model group, the Tianmu Jiangya powder administration group could continuously reduce SBP in SHR rats, maintain HR stability (P<0.05), significantly increase the claw of r value, lower the claw of g value(P<0.05). LVEF, FS significantly increased, LVEDV, LVESV, LVIDd and LVIDs significantly decreased (P<0.05), significantly increased serum NO content, decreased liver weight, liver weight/tibia length, plasma MN, UREA, UA content (P<0.05), and down-regulated the expression of iNOS and VEGF protein in the aorta(P<0.05). Conclusion::Tianmu Jiangya powder has a certain antihypertensive effect, and its mechanism may be mainly related to protecting heart function, improving vascular endothelial function, reducing catecholamines and sedative analgesia.