The FMS-like tyrosine kinase 3 (FLT3) gene mutation is the most common genetic mutation in acute myeloid leukemia (AML) and is associated with poor prognosis. Various targeted inhibitors have been developed for FLT3 mutations and have shown promising clinical efficacy. However, the emergence of resistance poses new challenges for targeted therapy in AML. This article provides an overview of the pathological and prognostic role of FLT3 mutations in AML, the current research progress on commonly used FLT3 inhibitors (type I and type II), the mechanisms of FLT3 inhibitor resistance, and strategies for overcoming resistance.

Diffuse large B-cell lymphoma (DLBCL) can be caused by multiple factors, including virus and autoimmune function, which in turn trigger persistent activation of the B-cell receptor (BCR) signaling pathway and other related signaling pathways, which collectively promote malignant B-cell proliferation and lead to tumor formation. Studies have shown significant progress in the treatment of primary and relapsed/refractory DLBCL with Bruton tyrosine kinase inhibitor (BTKi) in combination with chemotherapy, immunotherapy and small molecule inhibitors in the setting of poor outcome with BTKi monotherapy. This article reviews the progress of BTKi combined regimens in DLBCL.

OBJECTIVE To study the pharmacokinetics of paeoniflorin， hesperidin， naringenin， formononetin and enoxolone from Chitong xiaoyanling granules in rats. METHODS Six male SD rats fasted but not deprived of water for 12 h were given Chitong xiaoyanling granules （5.0 g/kg） intragastrically at one time. Blood was collected from inner canthus of rats at different time points after administration. Plasma samples were pretreated with acetonitrile precipitated protein （sulfamethoxazole as internal standard）， and the concentrations of 5 ingredients in plasma were determined by liquid chromatography-tandem mass spectrometry （LC-MS/MS）. The pharmacokinetic parameters of each ingredient were calculated using DAS 3.0 software. RESULTS After intragastric administration of Chitong xiaoyanling granules， tmax and t1/2 of formononetin were the shortest among 5 ingredients （0.25 h and 0.39 h， respectively）. For naringenin and enoxolone， the tmax was shorter， but t1/2 was longer， and there was an obvious double-peak phenomenon in the drug-time curve of naringenin. Compared with the other three components， cmax and AUC of paeoniflorin and hesperidin were not directly proportional to the content of in vitro components. CONCLUSIONS Formononetin， naringin and enoxolone in Chitong xiaoyanling granules were absorbed rapidly in rats， while paeoniflorin and hesperidin were absorbed slowly.

Objective: To investigate the seroprevalence and influencing factors of serum neutralizing antibodies among SARS-CoV-2 infected individuals, so as to provide the evidence for developing the health management and COVID-19 vaccination strategy among SARS-CoV-2 infected individuals. Methods: Recovered SARS-CoV-2 infected individuals from January 1st, 2020 to February 10th, 2021 in Zhejiang Province were recruited in March 2021. Participants' demographics, underlying diseases, date of definitive diagnosis and severity of clinical symptoms were collected using questionnaire surveys, and serum neutralizing antibody against SARS-CoV-2 was detected using a fluorescent immunoassay. In addition, factors affecting the seropositivity of neutralizing antibody against SARS-CoV-2 were identified using a multivariable logistic regression model. Results: A total of 559 SARS-CoV-2 infected individuals were enrolled, including 480 confirmed cases and 79 asymptomatic carriers, with an median (interquartile range) age of 47.00 (22.00) years, and all participants had never received COVID-19 vaccination. The median (interquartile range) duration from diagnosis to serum sampling was 387.00 (11.00) days, and the seroprevalence of neutralizing antibody against SARS-CoV-2 was 83.90%. The serum neutralizing antibody against SARS-CoV-2 was all positive 9 months after diagnosis, and the seroprevalence of neutralizing antibody against SARS-CoV-2 appeared no tendency towards a decline with time within 14 months after diagnosis (P>0.05). Multivariable logistic regression analysis showed that women were 1.892 times (95%CI: 1.169-3.064) more likely to produce serum neutralizing antibodies against SARS-CoV-2 than men, and mild, common and severe/critically ill SARS-CoV-2 infected cases were 2.438 (95%CI: 1.305-4.557), 4.481 (95%CI: 2.318-8.663), and 23.525 (95%CI: 2.990-185.068) times more likely to produce serum neutralizing antibodies against SARS-CoV-2 than asymptomatic carrier, respectively. Conclusions The seroprevalence of neutralizing antibody was 100.00% among SARS-CoV-2 infected individuals within 9 months after diagnosis. Individuals' gender and severity of clinical symptoms correlate with the seroprevalence of neutralizing antibody against SARS-CoV-2.

Objective:To explore the effects of habit reversal training on the use of inhaled corticosteroids (ICS) in patients with bronchial asthma.Methods:Select 89 patients with bronchial asthma using ICS admitted to the respiratory department of the Anhui No.2 Provincial People′s Hospital from 2016 January - 2019 January, and they were randomly divided into control group and study group, 45 cases in control group and 44 cases in study group. Patients in the control group received usual care and propaganda measures, the patients in the study group were intervened by the behavioral habit reversal training consisting of consciousness practice, behavior evaluation, antagonistic action training, anxiety management, follow-up and social support.. Asthma control test questionnaire (ACT), self-developed evaluation method of ICS inhalation technique, bronchial asthma quality of life questionnaire (AQLQ), were used to evaluate the difference of inhaled glucocorticoid corticosteroid therapy before and after the intervention.Results:The ICS inhalation technique scores (6.24±0.82) were higher than those of the control group (4.13±0.67), the difference was statistically significant ( t=-13.307, P<0.05). ACT scores of the study group were better than those of the control group ( Z=-2.780, P=0.005), the difference was statistically significant ( P<0.05). After intervention, AQLQ total scores in the study group, and the asthma symptoms, psychological status, and scores of the self-health dimension in AQLQ in the study group were (211.74±29.84), (51.09±6.49), (39.57±5.24), (24.36±3.41), higher than those in the control group(191.18±27.91), and (43.18±5.73), (31.21±4.62), (19.94±2.84), the difference was statistically significant ( t value was -7.988 - -3.358, P<0.05). Conclusion:Habit reversal training can effectively enhance the technical level of bronchial asthma patients operating ICS device, further improve the status of asthma control, improve the quality of life of patients, and improve the quality of nursing services for such patients.

Objective:To evaluate the effect of remote ischemic conditioning (RIC) on left ventricular (LV) myocardial perfusion, myocardial viability, LV remodeling, regional and global LV function serially following acute myocardial infarction (AMI) in Chinese mini-pigs.Methods:AMI was established in 12 Chinese mini-pigs (8 males, 4 females; age: 6-8 months) and they were randomly divided into RIC group ( n=6) and non-RIC group ( n=6). RIC was performed in pigs by blood pressure inflation on the lower limbs for 5 min period and 4 cycles immediately after surgery. A series of myocardial perfusion imaging and gated 18F-fluorodeoxyglucose (FDG) myocardial metabolism PET/CT imaging were performed longitudinally at the 1st, 14th, 28th and 56th days after AMI, and parameters including total perfusion defect (TPD), hibernating myocardium (HM), Scar, left ventricular ejection fraction (LVEF), left ventricular end-diastolic volume (LVEDV), left ventricular end-systolic volume (LVESV), summed motion score (SMS), summed thickening score (STS) and changes of these parameters were obtained. Independent-samples t test and Mann-Whitney U test were used to analyze data. Results:Nine Chinese mini-pigs survived after surgery and were performed imaging. Compared to non-RIC group ( n=4), HM at the 28th ((6.0±2.4)% vs (17.0±4.6)%; t=-4.158), TPD 14th-1st ((-11.8±5.4)% vs 9.0%(4.5%, 15.0%); z=2.449), TPD 28th-1st ((-15.3±3.9)% vs (12.0±3.0)%; t=-10.071), TPD 56th-1st ((-18.0±6.5)% vs 9.0%(4.5%, 12.0%); z=2.449), HM 28th-1st ((-10.5±6.9)% vs (8.3±2.1)%; t=-4.507), HM 56th-1st (-15.0%(-17.5%, -8.5%) vs 2.0%(0%, 7.0%); z=2.449) and LVEDV 14th-1st (-0.5(-2.5, 0) ml vs (13.0±4.4) ml; z=2.470) were reduced in RIC group ( n=5; all P<0.05). Conclusion:RIC can improve myocardial perfusion, delay LV remodeling in the acute stage and salvage hibernating myocardium in the subacute stage and chronic stage.

Objective:To describe our experiences in application of the 2019 revision of "CCCG-WT-2016" for the diagnosis of Wilms tumors.Methods:Ninety-one cases of Wilms tumor diagnosed at Shanghai Children′s Medical Center from January 2015 to December 2018 were collected. All cases were reviewed by two senior pathologists, including one from China and the other from Singapore, according to the 2019 revision of "CCCG-WT-2016."Results:The specimens were obtained by core biopsy ( n=21), primary nephrectomy ( n=41), post-chemotherapy nephrectomy/resection ( n=18), or biopsy/resection of metastatic/relapse/post-chemotherapy metastatic lesion(s) ( n=11). The specimens of core biopsy and primary nephrectomy ( n=62) all had favorable histology.Twelve post-chemotherapy nephrectomy cases were subdivided into three risk groups: low risk ( n=0), intermediate risk ( n=10) and high risk ( n=2). Six post-chemotherapy resection cases were subdivided into 3 risk groups:low risk ( n=0), intermediate risk ( n=5) and high risk ( n=1). The remaining 11 cases were comprised of metastatic, relapse, and post-chemotherapy metastatic lesions. The concordance rate of the two senior pathologists was 100%(91/91). Conclusions:The 2019 revision of "CCCG-WT-2016" is clearly written and easy to use. It can serve as the basis of accurate classification for clinical treatment.

Objective: Victims with shock-able initial arrest rhythms (ventricular fibrillation or pulse-less ventricular tachycardia, VF/VT) have much better outcomes from out-of-hospital cardiac arrest (OHCA) than those with non-shock-able initial rhythms (pulse-less electrical activities, PEA or asystole). Prompt defibrillation is believed pivotal to terminate lethal shock-able arrest rhythms. In this study, we were to identify those pre-hospital epidemiological factors which were associated with likelihood of shock-able rhythms first recorded when out-of-hospital cardiac arrest occurred. Methods: A multicenter, secondary, retrospective and observational analysis was performed on all adult non-traumatic OHCA in the Resuscitation Outcome Consortium (ROC) PRIMED study from June 2007 through November 2009. Of a total of 17 177 OHCA cases in PRIMED study, 13 421 of them were enrolled in this study when those OHCA patients with DNR order, or initial rhythms unknown, or arrest caused by obvious cause were excluded. We reported their demographics and episode characteristics for all enrolled cases. Multivariable logistic regression was employed to identify factors which were associated with likelihood of VF/VT recorded as shock-able initial rhythms. Results: Among 13 421 adult non-traumatic OHCA cases with initial rhythms recorded, 3 527 (26.3%) of them had shock-able rhythms, while 9 894 (73.7%) patients were in non-shock-able rhythms. Of the OHCA with shock-able arrest rhythms, 1 850(52.5%) obtained return of spontaneous circulation (ROSC) in the field, while 912 (25.9%) survived to hospital discharge. On the other hand, 2489(25.2%) of the OHCA with non-shock-able arrest rhythms obtained ROSC in the field, while 325 (3.3%) of them survived to hospital discharge. Multivariable regression analysis revealed those factors which indicated likelihood of shock-able rhythms recorded were: age(OR: 0.991,95%CI 0.988-0.993), male gender (OR1.887,95%CI1.718-2.073), pre-hospital Emergency Medical System(EMS) response time(OR0.950,95%CI 0.931-0.970), cardiac arrest witnessed by EMS providers(OR1.709,95%CI 1.423-2.054) or bystander(OR3.199,95%CI 2.921-3.504) and those with bystanders CPR (OR1.357,95%CI 1.239-1.487),public place of cardiac arrest (OR2.705,95%CI 2.437-3.003). Conclusions Some demographics and pre-hospital characteristics were proved associated with likelihood of shock-able arrest rhythms first recorded in OHCA victims, which might help develop corresponding strategies to deliver prompt shock on initially shock-able patients and improve their outcomes.

Objective To investigate the effect of sub-anesthesia dose of isoflurane in 60％ oxygen on acute lung injury in aged rats with sepsis.Methods Ninety male Sprague-Dawley rats,aged 12-14 months,weighing 500-800 g,were divided into 3 groups (n=30 each) using a random number table:sham operation group (Sham group),sepsis group (S group),and sepsis plus isoflurane plus oxygen treatment group (S+I+O group).Sepsis was induced by cecal ligation and puncture in S and S+I+O groups.In group S+I+O,0.7％ isoflurane in 60％ oxygen was inhaled for 1 h starting from 1 and 6 h after operation.Eighteen rats were selected in each group and observed for 7 days after operation,and the survival rate was recorded.Six rats were selected in each group at 24 h after operation,and bronchoalveolar lavage fluid (BALF) was collected to determine the protein concentrations (by BCA protein assay),blood samples were collected from the femoral artery for blood gas analysis,PaO2 was recorded,and the oxygenation index was calculated.Six rats in each group were sacrificed at 24 h after operation,the left lung specimens were obtained and stained with hematoxylin and eosin for examination of pathological changes,the right lung specimens were obtained for determination of wet to dry weight ratio (W/D ratio),and blood samples were collected from the right atrium for measurement of the concentrations of interleukin-1β (IL-1β),IL-6,tumor necrosis factor-α (TNF-α),high-mobility group box 1 protein (HMGB1) and IL-10 in serum (by enzyme-linked immunosorbent assay).Results Compared with group Sham,the survival rate was significantly decreased,and the concentrations of IL-1β,IL-6,TNF-α,HMGB1 and IL-10 in serum were increased in S and S+I+O groups,and W/D ratio and protein concentrations in BALF were significantly increased,and the oxygenation index was decreased in group S (P＜0.05).Compared with group S,the survival rate was significantly increased,W/D ratio and protein concentrations in BALF were decreased,the oxygenation index was increased,the concentrations of IL-1β,IL-6,TNF-α and HMGB1 in serum were decreased,and the concentration of serum IL-10 was increased (P＜0.05),and the pathological changes were significantly attenuated in group S+I+O.Conclusion Sub-anesthesia dose of isoflurane in 60％ oxygen can reduce acute lung injury in aged rats with sepsis,and the mechanism may be ralated to inhibiting systemic inflammatory responses.

Objective To preliminarily investigate the protective effect of chronic clonorchis sinesis(Cs) infestation against sepsis in Sprague Dawley(SD) rats in order to explore its underlying mechanism.Methods Chronic Cs infestation model of SD rats was reproduced by intra-gastric administration with Cs ova.Twenty rats were randomly(random number) divided into normal group(n=10) and Cs group(n=10).The proportion of differentiation in M1 and M2 macrophages were detected by flow cytometry.The expressions of Arg-1(arginine-1),FIZZ 1,iNOs and TNF-αmRNA were examined by reverse transcriptase polymerase chain reaction(RT-PCR).The cecal ligation and puncture(CLP) procedure was performed to reproduce sepsis model of SD rats.Sixty rats were randomly(random number) divided into control group,SHAM group,CLP group,Mφ+CLP group,Cs-Mφ+CLP group,and Cs-CLP group.The cumulative mortalities were calculated.The pathological changes of the lung tissue in different groups were demonstrated by HE staining.The serum levels of cytokines TNF-α and IL-10 were detected by ELISA at 0,24,48 and 72 h after CLP procedure.Results Compared with M1 peritoneal macrophages differentiation in control group(91.9%),rat peritoneal macrophages were activated to M2 differentiation(95.1%) in chronic Cs infection group.RT-PCR assay showed expression of Arg-1 and FIZZ 1 mRNA were higher in M2 macrophages,and on the contrary, the expression of iNOS mRNA expression was higher in M1 macrophages.The expression of TNF-α mRNA in M1 was significantly higher than that in M2, whereas the expression of IL-10 mRNA in M2 was higher than that in M1.The cumulative mortality of septic rats 72 h after CLP procedure were much lower in both chronic Cs infestation group and M2 macrophages adoptive transfer group(CLP group 70%vs.Mφ+CLP group 50%vs.Cs-Mφ+CLP group 30%vs.Cs-CLP group 0%,P<0.05).In these two groups,the pathological damages in lung tissues were significantly improved.The serum level of TNF-α was decreased and the anti-inflammatory IL-10 level was increased significantly in these two groups with Cs compared with other groups.Conclusion M2 macrophages polarization induced by chronic Cs infestation with M2 phenotype gene and expression of anti-inflammatory cytokine gene play key role in increasing anti-inflammatory cytokines and decreasing pro-inflammatory cytokines to allerviate organ damage and ameliorating the survival rate in septic rats.