Objective: To analyze and compare therapy responses, outcomes, and incidence of severe hematologic adverse events of flumatinib and imatinib in patients newly diagnosed with chronic phase chronic myeloid leukemia (CML) . Methods: Data of patients with chronic phase CML diagnosed between January 2006 and November 2022 from 76 centers, aged ≥18 years, and received initial flumatinib or imatinib therapy within 6 months after diagnosis in China were retrospectively interrogated. Propensity score matching (PSM) analysis was performed to reduce the bias of the initial TKI selection, and the therapy responses and outcomes of patients receiving initial flumatinib or imatinib therapy were compared. Results: A total of 4 833 adult patients with CML receiving initial imatinib (n=4 380) or flumatinib (n=453) therapy were included in the study. In the imatinib cohort, the median follow-up time was 54 [interquartile range (IQR), 31-85] months, and the 7-year cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) were 95.2%, 88.4%, 78.3%, and 63.0%, respectively. The 7-year FFS, PFS, and OS rates were 71.8%, 93.0%, and 96.9%, respectively. With the median follow-up of 18 (IQR, 13-25) months in the flumatinib cohort, the 2-year cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) were 95.4%, 86.5%, 58.4%, and 46.6%, respectively. The 2-year FFS, PFS, and OS rates were 80.1%, 95.0%, and 99.5%, respectively. The PSM analysis indicated that patients receiving initial flumatinib therapy had significantly higher cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) and higher probabilities of FFS than those receiving the initial imatinib therapy (all P<0.001), whereas the PFS (P=0.230) and OS (P=0.268) were comparable between the two cohorts. The incidence of severe hematologic adverse events (grade≥Ⅲ) was comparable in the two cohorts. Conclusion: Patients receiving initial flumatinib therapy had higher cumulative incidences of therapy responses and higher probability of FFS than those receiving initial imatinib therapy, whereas the incidence of severe hematologic adverse events was comparable between the two cohorts.
Adult ; Humans ; Adolescent ; Imatinib Mesylate/adverse effects* ; Incidence ; Antineoplastic Agents/adverse effects* ; Retrospective Studies ; Pyrimidines/adverse effects* ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy* ; Treatment Outcome ; Benzamides/adverse effects* ; Leukemia, Myeloid, Chronic-Phase/drug therapy* ; Aminopyridines/therapeutic use* ; Protein Kinase Inhibitors/therapeutic use*

OBJECTIVES: To investigate the clinical treatment outcomes and the changes of the outcomes over time in extremely preterm twins in Guangdong Province, China. METHODS: A retrospective analysis was performed for 269 pairs of extremely preterm twins with a gestational age of <28 weeks who were admitted to the department of neonatology in 26 grade A tertiary hospitals in Guangdong Province from January 2008 to December 2017. According to the admission time, they were divided into two groups: 2008-2012 and 2013-2017. Besides, each pair of twins was divided into the heavier infant and the lighter infant subgroups according to birth weight. The perinatal data of mothers and hospitalization data of neonates were collected. The survival rate of twins and the incidence rate of complications were compared between the 2008-2012 and 2013-2017 groups. RESULTS: Compared with the 2008-2012 group, the 2013-2017 group (both the heavier infant and lighter infant subgroups) had lower incidence rates of severe asphyxia and smaller head circumference at birth (P<0.05). The mortality rates of both of the twins, the heavier infant of the twins, and the lighter infant of the twins were lower in the 2013-2017 group compared with the 2008-2012 group (P<0.05). Compared with the 2008-2012 group, the 2013-2017 group (both the heavier infant and lighter infant subgroups) had lower incidence rates of pulmonary hemorrhage, patent ductus arteriosus (PDA), periventricular-intraventricular hemorrhage (P-IVH), and neonatal respiratory distress syndrome (NRDS) and a higher incidence rate of bronchopulmonary dysplasia (P<0.05). CONCLUSIONS There is a significant increase in the survival rate over time in extremely preterm twins with a gestational age of <28 weeks in the 26 grade A tertiary hospitals in Guangdong Province. The incidences of severe asphyxia, pulmonary hemorrhage, PDA, P-IVH, and NRDS decrease in both the heavier and lighter infants of the twins, but the incidence of bronchopulmonary dysplasia increases. With the improvement of diagnosis and treatment, the multidisciplinary collaboration between different fields of fetal medicine including prenatal diagnosis, obstetrics, and neonatology is needed in the future to jointly develop management strategies for twin pregnancy.
Bronchopulmonary Dysplasia/epidemiology* ; Female ; Gestational Age ; Humans ; Infant ; Infant, Extremely Premature ; Infant, Newborn ; Pregnancy ; Respiratory Distress Syndrome, Newborn/epidemiology* ; Retrospective Studies ; Treatment Outcome

OBJECTIVE: To explore the role of P2X7 receptor (P2X7R) in migration and invasion of mouse Lewis lung cancer (LLC) cells and examine the tumorigenic ability of LLC cells in P2X7R-knockout mice. METHODS: RT-PCR was used to examine P2X7R mRNA expression in LLC cells. LLC cells were treated with ATP (as a P2X7R agonist) or 2'- 3'- O- (4-benzoyl- benzoyl)-ATP (BzATP) (a P2X7R agonist) with or without pretreatment with P2X7R antagonist oxATP or A438079. The changes in migration and invasive abilities of the cells were evaluated using wound healing assay and Transwell assay; Western blotting was performed to determine the activation level of the key proteins in the AKT signaling pathway. The effects of BzATP, A438079, and LY294002 (a inhibitor of the PI3K/AKT pathway) on migration and invasion of LLC cells were also examined. In wild-type (WT) and P2X7R knockout (P2X7^-/-) C57BL/6 mice, the growth of subcutaneous LLC cell xenografts were observed by measuring tumor volume and weight. RESULTS: P2X7R expression was detected in LLC cells. Treatment with P2X7R agonist significantly enhanced migration and invasion abilities of LLC cells, and this effect was inhibited by application of P2X7R antagonists (P < 0.001). Western blotting showed that BzATP treatment of LLC cells significantly increased the expression level of p-AKT protein, which was obviously lowered by treatment with P2X7R antagonist (P < 0.01). P2X7R antagonist strongly inhibited BzATP-induced enhancement of LLC cell migration and invasion (P < 0.001). In the tumor- bearing mice, the tumor volume and weight were significantly lower in P2X7^-/- mice than in WT mice (P < 0.05). CONCLUSION P2X7R promotes migration and invasion of LLC cells by activating the AKT signaling pathway, and LLC cells show lowered tumorigenic capacity in P2X7^-/- mice.
Humans ; Mice ; Animals ; Receptors, Purinergic P2X7 ; Proto-Oncogene Proteins c-akt/metabolism* ; Phosphatidylinositol 3-Kinases/metabolism* ; Mice, Inbred C57BL ; Signal Transduction ; Adenosine Triphosphate/metabolism* ; Lung Neoplasms

During the coronavirus disease (COVID-19) epidemic, there have been concerns about the impact of vaccines on people's fertility, including the fertility of those who are currently preparing for pregnancy and those who might become pregnant in future. However, there is still a lack of research on the effect of the COVID-19 vaccine on male fertility, and it is not surprising that couples and donors have concerns regarding vaccination. In this study, a retrospective cohort study was conducted to examine semen quality before and after receipt of the inactivated COVID-19 vaccine. There were no statistically significant changes in semen parameters (volume, sperm concentration, progressive motility, and total progressive motile count) after two doses of vaccine (all P > 0.05). In summary, our study updates the most recent studies on the effects of the COVID-19 vaccine on male fertility, and the information from this study could be used to guide fertility recommendations for assisted reproductive technology (ART) patients and donors.
COVID-19 ; COVID-19 Vaccines ; Female ; Humans ; Male ; Pregnancy ; Retrospective Studies ; Semen ; Semen Analysis ; Sperm Count ; Sperm Motility ; Spermatozoa ; Vaccination ; Vaccines, Inactivated

OBJECTIVE: To evaluate the clinical characteristics, treatment and prognosis of systemic anaplastic large cell lymphoma(sALCL). METHODS: The clinical data of 90 cases with sALCL treated in the Department of Hematology of the Affiliated Xijing Hospital of Air Force Medical University from November 2018 to October 2021 were retrospectively analyzed. The clinical features, treatment and prognosis were summarized and the prognostic factors were investigated. RESULTS: There were 58 males and 32 females, with a median age of 32 (12-73) years old. 69 (76.7%) patients had Ann Arbor stage Ⅲ-Ⅳ disease and half of the patients had extranodal infiltration. The median age was 27(12-72) years of the 60 ALK⁺ patients while 53(15-73) years of the 30 ALK^- patients, and it was significantly different in the age of onset between the two group(P<0.01). 88 patients received first line chemotherapy, and 50(568%) cases achieved complete remission(CR). IPI score≥3 was an independent risk factor for CR. The median progressive free survival(PFS) and overall survival(OS) of the patients were not reached. Multivariate analysis showed that no achievement of CR after first-line therapy was a significant prognostic factor influencing PFS and OS. CONCLUSION sALCL mainly occurs in males and most patients were in advanced stage. Half of the patients had extranodal involvement. The CR rate after first-line chemotherapy was 568%, and IPI score≥3 was a significant prognostic factor for CR. No achievement of CR after first-line therapy is poorly prognostic for PFS and OS.
Adolescent ; Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Child ; Disease-Free Survival ; Female ; Humans ; Lymphoma, Large-Cell, Anaplastic/diagnosis* ; Male ; Middle Aged ; Prognosis ; Receptor Protein-Tyrosine Kinases ; Retrospective Studies ; Young Adult

Objective: To analyze the clinical epidemiological characteristics including composition of pathogens , clinical characteristics, and disease prognosis acute bacterial meningitis (ABM) in Chinese children. Methods: A retrospective analysis was performed on the clinical and laboratory data of 1 610 children <15 years of age with ABM in 33 tertiary hospitals in China from January 2019 to December 2020. Patients were divided into different groups according to age,<28 days group, 28 days to <3 months group, 3 months to <1 year group, 1-<5 years of age group, 5-<15 years of age group; etiology confirmed group and clinically diagnosed group according to etiology diagnosis. Non-numeric variables were analyzed with the Chi-square test or Fisher's exact test, while non-normal distrituction numeric variables were compared with nonparametric test. Results: Among 1 610 children with ABM, 955 were male and 650 were female (5 cases were not provided with gender information), and the age of onset was 1.5 (0.5, 5.5) months. There were 588 cases age from <28 days, 462 cases age from 28 days to <3 months, 302 cases age from 3 months to <1 year of age group, 156 cases in the 1-<5 years of age and 101 cases in the 5-<15 years of age. The detection rates were 38.8% (95/245) and 31.5% (70/222) of Escherichia coli and 27.8% (68/245) and 35.1% (78/222) of Streptococcus agalactiae in infants younger than 28 days of age and 28 days to 3 months of age; the detection rates of Streptococcus pneumonia, Escherichia coli, and Streptococcus agalactiae were 34.3% (61/178), 14.0% (25/178) and 13.5% (24/178) in the 3 months of age to <1 year of age group; the dominant pathogens were Streptococcus pneumoniae and the detection rate were 67.9% (74/109) and 44.4% (16/36) in the 1-<5 years of age and 5-<15 years of age . There were 9.7% (19/195) strains of Escherichia coli producing ultra-broad-spectrum β-lactamases. The positive rates of cerebrospinal fluid (CSF) culture and blood culture were 32.2% (515/1 598) and 25.0% (400/1 598), while 38.2% (126/330)and 25.3% (21/83) in CSF metagenomics next generation sequencing and Streptococcus pneumoniae antigen detection. There were 4.3% (32/790) cases of which CSF white blood cell counts were normal in etiology confirmed group. Among 1 610 children with ABM, main intracranial imaging complications were subdural effusion and (or) empyema in 349 cases (21.7%), hydrocephalus in 233 cases (14.5%), brain abscess in 178 cases (11.1%), and other cerebrovascular diseases, including encephalomalacia, cerebral infarction, and encephalatrophy, in 174 cases (10.8%). Among the 166 cases (10.3%) with unfavorable outcome, 32 cases (2.0%) died among whom 24 cases died before 1 year of age, and 37 cases (2.3%) had recurrence among whom 25 cases had recurrence within 3 weeks. The incidences of subdural effusion and (or) empyema, brain abscess and ependymitis in the etiology confirmed group were significantly higher than those in the clinically diagnosed group (26.2% (207/790) vs. 17.3% (142/820), 13.0% (103/790) vs. 9.1% (75/820), 4.6% (36/790) vs. 2.7% (22/820), χ²=18.71, 6.20, 4.07, all P<0.05), but there was no significant difference in the unfavorable outcomes, mortility, and recurrence between these 2 groups (all P>0.05). Conclusions: The onset age of ABM in children is usually within 1 year of age, especially <3 months. The common pathogens in infants <3 months of age are Escherichia coli and Streptococcus agalactiae, and the dominant pathogen in infant ≥3 months is Streptococcus pneumoniae. Subdural effusion and (or) empyema and hydrocephalus are common complications. ABM should not be excluded even if CSF white blood cell counts is within normal range. Standardized bacteriological examination should be paid more attention to increase the pathogenic detection rate. Non-culture CSF detection methods may facilitate the pathogenic diagnosis.
Adolescent ; Brain Abscess ; Child ; Child, Preschool ; Escherichia coli ; Female ; Humans ; Hydrocephalus ; Infant ; Infant, Newborn ; Male ; Meningitis, Bacterial/epidemiology* ; Retrospective Studies ; Streptococcus agalactiae ; Streptococcus pneumoniae ; Subdural Effusion ; beta-Lactamases

Objective:To investigate the bacterial composition and antimicrobial resistance profile of clinical isolates from bloodstream infections in China.Methods:The clinical bacterial strains isolated from blood culture were collected during January 2020 to December 2020 in member hospitals of Blood Bacterial Resistant Investigation Collaborative System (BRICS). Antibiotic susceptibility tests were conducted by agar dilution or broth dilution methods recommended by Clinical Laboratory Standards Institute(CLSI, USA). WHONET 5.6 was used to analyze data.Results:During the study period, 10 043 bacterial strains were collected from 54 hospitals, of which 2 664 (26.5%) were Gram-positive bacteria and 7 379 (73.5%) were Gram-negative bacteria. The top 10 bacterial species were Escherichia coli (38.6%), Klebsiella pneumoniae (18.4%), Staphylococcus aureus (9.9%), coagulase-negative Staphylococci (7.5%), Pseudomonas aeruginosa (3.9%), Enterococcus faecium (3.3%), Enterobacter cloacae (2.8%), Enterococcus faecalis (2.6%), Acinetobacter baumannii (2.4%) and Klebsiella spp (1.8%). The prevalence of methicillin-resistant Staphylococcus aureus (MRSA) and methicillin-resistant coagulase-negative Staphylococcus aureus were 27.6% and 74.4%, respectively. No glycopeptide- and daptomycin-resistant Staphylococci were detected. More than 95% of Staphylococcus aureus were sensitive to rifampicin and SMZco. No vancomycin-resistant Enterococci strains were detected. Extended spectrum β-lactamase (ESBL) producing Escherichia coli, Klebsiella pneumoniae and Proteus mirabilis were 48.4%, 23.6% and 36.1%, respectively. The prevalence rates of carbapenem-resistance in Escherichia coli and Klebsiella pneumoniae were 2.3% and 16.1%, respectively; 9.6% of carbapenem-resistant Klebsiella pneumoniae strains were resistant to ceftazidime/avibactam combination. The prevalence rate of carbapenem-resistance in Acinetobacter baumannii was 60.0%, while polymyxin and tigecycline showed good activity against Acinetobacter baumannii. The prevalence rate of carbapenem-resistance of Pseudomonas aeruginosa was 23.2%. Conclusions:The surveillance results in 2020 showed that the main pathogens of bloodstream infection in China were gram-negative bacteria, while Escherichia coli was the most common pathogen, and ESBL-producing strains declined while carbapenem-resistant Klebsiella pneumoniae kept on high level. The proportion and the prevalence of carbapenem-resistant Pseudomonas aeruginosa were on the rise slowly. On the other side, the MRSA incidence got lower in China, while the overall prevalence of vancomycin-resistant Enterococci was low.

Scutellariae Radix is a kind of traditional Chinese medicine, which has the functions of heat-clearing and damp-drying, purging fire and detoxifying, hemostasis and miscarriage prevention. Modern pharmacological studies show that Scutellariae Radix has various effects, such as anti-oxidation, anti-inflammatory, liver protection and antiviral microorganisms. By searching the documents in the past ten years, the author has found that Scutellariae Radix and its active components play an important role in protecting the liver. It can prevent and cure liver injuries caused by different reasons, including acute or chronic hepatitis, liver fibrosis and liver cancer. Among all kinds(chemical, immunological, alcoholic, nonalcoholic, viral, ischemia-reperfusion, etc.) of acute or chronic hepatitis, most studies are on CCl_4 induced chemical liver injury. Scutellariae Radix and its active components can significantly reduce the serum transaminase level in hepatitis animals, and reduce the degree of liver pathological damage. The mechanisms include antioxidant stress, anti-inflammatory, anti-apoptosis, inhibition of immunity, anti-virus and regulation of lipid metabolism, etc. Scutellariae Radix and its active components can significantly inhibit the activation of hepatic stellate cells and reduce extracellular matrix, and its anti-fibrosis mechanism involves antioxidation, anti-inflammatory, inducing apoptosis of hepatic stellate cells and so on. Whether in vivo or in vitro, Scutellariae Radix and its active components show a good anti-hepatocarcinoma effect, especially on hepatocarcinoma. Its prevention and treatment mechanisms for hepatocarcinoma mainly include blocking cancer cell cycle, inhibiting cancer cell metastasis, promoting cancer cell apoptosis and inducing autophagy. It can be seen that Scutellariae Radix has multiple functions and mechanisms in liver protection, and has a great development potential. Therefore, this paper reviews the prevention and treatment effects and mechanism of Scutellariae Radix and its components on different liver diseases, in order to provide reference for in-depth study, development and clinical application in the prevention and treatment of liver disease.
Animals ; Anti-Inflammatory Agents ; Drugs, Chinese Herbal ; Flavonoids ; Medicine, Chinese Traditional ; Scutellaria baicalensis

Objective: To investigate the application and efficacy of left ventricular (LV) electrical delay (LVED) and the distance of right ventricular(RV) pacing polar to LV(DRLV) in optimizing LV pacing polar. Methods: Heart failure (HF) patients who implanted cardiac resynchronization therapy (CRT) device with a LV quadripolar lead from January 2014 to January 2018 at General Hospital of Northern Theater Command were enrolled in the study. Measurements of LVED and DRLV of each polar of the lead were performed in patients with HF who underwent CRT with LV quadripolar lead. The principle in turn for polar selecting used for clinical LV pacing was the pacing polar: (1)without phrenic nerve stimulation(PNS); (2)with appropriate capture threshold; (3)not located in apical; (4)with maximal LVED; (5)with maximal DRLV. The LV pacing polar was selected for CRT according to the procedure. The distribution of target veins implanted with LV quadripolar lead were calculated. The percentage of biventricular pacing at 6-month follow-up was recorded. The following indexes were compared before and 6-month after surgery, including QRS duration, LV end-systolic volume(LVESV), LV ejection fraction(LVEF), LV end-diastolic dimension(LVEDD), 6 minute walking distance(6MWD), New York Heart Association(NYHA) class. The efficacy and echocardiographic efficacy of CRT was evaluated. Results: There were twenty-nine HF patients enrolled. The mean age of enrolled patients was(61.7±7.6)years old, nineteen (66%)of them were male. There were seventeen(59%) patients diagnosed as dilated cardiomyopathy and twelve(41%) patients as ischemic cardiomyopathy. All patients were successfully implanted with LV quadripolar lead into target veins, and all four pacing sites were also in target veins. Target veins were located in lateral veins in 15 patients (52%), anterior veins in 2 patients (7%), posterior veins in 11 patients (38%), and lateral branches of great cardiac veins in 1 patient (3%). After 6-month of follow-up, the percentage of biventricular pacing was greater than 95%.There were nineteen(66%) patients optimized LV pacing polar by the largest LVED and four (14%) patients by the DRLV. Of the 29 patients, 5(17%) patients used D1 as the pacing polar, 5(17%) patients used M2 as the pacing polar, 7(24%) patients used M3 as the pacing polar, and 12(41%) patients used P4 as the pacing polar. The pacing polars (D1, M2) of traditional bipolar lead were used in 10(34%) patients, and the LV quadripolar lead specific pacing polars (M3, P4) were used in 19(66%) patients.Compared to a LV quadripolar lead, the LV pacing polar (M3, P4) selected in 19(66%) patients were not achievable with the traditional LV bipolar lead (D1, M2). Preoperative QRS duration, LVESV, LVEF, LVEDD, 6MWD and NYHA class were (171±24)ms, (231±79)ml, (28±5)%, (74±11)mm, (294±103)m, (3.2±1.0)class and the postoperative 6-month were (130±12)ms, (158±73)ml, (36±10)%, (66±12)mm, (371±86)m, (1.9±0.5)class. These indexes were significantly improved after 6 months operation(P<0.001). 97% and 83% patients were responders of CRT as assessed by 6-month efficacy and echocardiographic efficacy. Conclusion: The maximal LVED and DRLV can be used to select LV pacing polar with a high rate of CRT response rate.
Aged ; Cardiac Resynchronization Therapy ; Heart Failure/therapy* ; Heart Ventricles ; Humans ; Male ; Middle Aged ; Treatment Outcome ; Ventricular Function, Left

De-etiolation consists of a series of developmental and physiological changes that a plant undergoes in response to light. During this process light, an important environmental signal, trig-gers the inhibition of mesocotyl elongation and the production of photosynthetically active chloro-plasts, and etiolated leaves transition from the'sink"stage to the'source"stage. De-etiolation has been extensively studied in maize (Zea mays L.). However, little is known about how this transition is regulated. In this study, we described a quantitative proteomic and phosphoproteomic atlas of the de-etiolation process in maize. We identified 16,420 proteins in proteome, among which 14,168 pro-teins were quantified. In addition, 8746 phosphorylation sites within 3110 proteins were identified. From the combined proteomic and phosphoproteomic data, we identified a total of 17,436 proteins. Only 7.0％(998/14,168) of proteins significantly changed in abundance during de-etiolation. In con-trast, 26.6％ of phosphorylated proteins exhibited significant changes in phosphorylation level;these included proteins involved in gene expression and homeostatic pathways and rate-limiting enzymes involved in photosynthetic light and carbon reactions. Based on phosphoproteomic anal-ysis, 34.0％(1057/3110) of phosphorylated proteins identified in this study contained more than 2phosphorylation sites, and 37 proteins contained more than 16 phosphorylation sites, indicating that multi-phosphorylation is ubiquitous during the de-etiolation process. Our results suggest that plants might preferentially regulate the level of posttranslational modifications (PTMs) rather than protein abundance for adapting to changing environments. The study of PTMs could thus better reveal the regulation of de-etiolation.